Cancer is a leading cause of suffering and death throughout the world and is expected to increase in prevalence as modern technologies extend life expectancy. Occasionally over the lifetime of a cell there are slight alternations made to the DNA known as mutations. Some of these mutations, known as ‘silent mutations’, do not result in any physical changes to the function of the cells but others can change the way a cell behaves.
A number of mechanisms exist to prevent a cell in which a mutation has occurred from proceeding in the cell cycle, and if the genetic error is not corrected, the cell will “commit suicide” in a process known as apoptosis. However, if a mutation occurs in a protein involved in cell cycle regulation, this can lead to uncontrolled proliferation of cells, known as neoplasia, which in turn may progress to cancer.
Cancer cells typically have an adverse effect on the body. The cancer can spread by invasion of adjacent tissues by malignant neoplastic tumor cells, and by a process known as metastasis, where the malignant cells dissociate from the tumour mass and spread to distant sites. Cancer manifests itself in a wide variety of forms, in many different types of tissue and is can be characterised by its degree of invasiveness and aggressiveness.
Cancer may be treated in a number of ways including surgery, radiation therapy and chemotherapy. The exact type of therapy used may depend on one or more of a number of factors, such as, what stage the cancer has reached, whether and where it has spread to and what the likely effects on lifestyle may be.
Various treatment methods may be used in concert to achieve improved therapy. For example, a tumour may be surgically removed and chemotherapy or radiation therapy then used to target remaining cancer cells. However, the various methods may be used alone with good results.
Chemotherapy involves the administration of drugs often targeted to rapidly dividing cells. Many chemotherapeutic drugs interfere with DNA replication prior to cell division. Although there have been many advances in chemotherapeutic agents, the genetic instability of cancer cells, especially advanced cancers, leads to a high incidence of drug resistant cancers and even multi-drug resistance (MDR).
Two favoured chemotherapeutic agents, taxol and cisplatin are used in combination to treat stage IV, the most advanced stage, and recurrent disease. As would be appreciated, failure to respond to either of these agents, or indeed the combination of both, leaves oncologists with limited therapeutic options going forward.
It would be useful if a therapeutic agent or combination of agents were available to treat therapy resistant cancers.
It is therefore an object of the present invention to provide agents useful in the treatment of therapy-resistant cancers.